Cystic fibrosis is a genetic disease that causes a thick, sticky mucus to build up in the lungs and digestive tract. A clinical trial of a new drug called denufosol found that those given the medication for six months prevented some of the accumulation and improved performance on lung tests.

The Cystic Fibrosis Foundation estimates that about 30,000 children and adults in the United States have the condition that clogs the lungs and leads to life-threatening lung infections. The mucus also obstructs the pancreas and stops natural enzymes from helping the body break down and absorb food.

Frank J. Accurso MD of the University of Colorado and colleagues included about 350 children with cystic fibrosis aged five and older in the study called TIGER-1, The Transport of Ions to Generate Epithelial Rehydration. All had a forced expiratory volume (FEV1) at least 75% of normal, indicating normal to mildly impaired lung function characteristic of early cystic fibrosis.

The patients were randomized to receive either 60 milligrams of inhaled denufosol three times daily or a matching placebo for 24 weeks. This was followed by another 24-week open-label safety extension phase.

The patients on the new medication had increase in FEV1 of 0.048 L, approximately 2% over baseline. In addition, the researchers found further lung improvement by 0.115L by the end of the open-label phase. The placebo group, when switched over to denofusol in the open-label phase, also improved by a mean 0.078 L in FEV1.

Big improvements weren't expected, says Accurso, because the drug is primarily designed to prevent or delay loss of lung function rather than act as a rescue therapy.

Denufosol appeared to be safe without serious adverse events or impaired growth of the young patients, suggesting it could be suitable as an early intervention. Intervention for cystic fibrosis early in its course has the potential to delay or prevent progressive changes that lead to irreversible airflow obstructions, the researchers say in their study published in the American Journal of Respiratory and Critical Care Medicine.

A second phase III trial, which is called TIGER-2, is ongoing which will incorporate a longer placebo-controlled treatment phase. Inspire Pharmaceuticals is targeting a potential US commercial launch of the drug for 2012, pending FDA approval.

Dr. Nick and his colleagues analyzed epidemiological and health data on 156 CF patients over 40 year of age who receive care at National Jewish Health, the largest adult cystic fibrosis clinic in the nation. In addition, data were analyzed on nearly 3,000 patients from around the nation who were included in the Cystic Fibrosis Foundation Patient Registry from 1992-2007.

The researchers found that the fate of females changes considerably in the older CF population. It has long been recognized that a “gender gap” is present in CF, favoring males. Historically, females have been diagnosed later, had a poorer prognosis, and survived fewer years than males.

Accordingly, Dr. Nick's analysis showed that fewer females diagnosed as children survived to age 40. However, among those diagnosed as adults, females represented a significant majority, accounting for 72 percent of patients in Colorado and 54 percent nationally. Among the adult diagnosed patients, females survived on average 9 to 14 years longer than males.

The complex factors that account for the differential fate of female CF patients is not understood, although Dr. Nick believes it could be a mixture of behavioral and biological factors.

Dr. Nick's findings also indicate that patients diagnosed as adults do not really have milder diseases — as is commonly believed — just a delayed onset of an equally severe form of the disease. Although patients diagnosed as adults live longer than those diagnosed as children, the adult-diagnosed patients lose lung function as rapidly those diagnosed in childhood, and approximately 85% die of respiratory failure or post-transplant complications.

Dr. Nick believes there is a significant number of adults whose CF remains undiagnosed. His analysis indicates that once those patients are accurately diagnosed, proper care can significantly improve their health. Patients diagnosed as adults and subsequently followed at a CF center reversed progressive lung function decline and improved their lung function for at least four years. Older patients commonly do not get specialized CF care. It is generally recognized that the team approach to treatment provided by the 112 CF Foundation-accredited Care Centers results in better clinical outcomes. However, less than half of long-term CF survivors continued to be seen at CF Centers as they pass 40 years, with the fewest among the adult-diagnosed patients.

“In the coming years, more and more cystic fibrosis patients will be living into their 40s, 50s and beyond,” said Dr. Nick. “Our findings concerning the role of gender, in survival, progression of disease, and type of care in current long-term survivors provides important insights that will help us prepare for better treatment of the steadily aging CF population.”